Different Numbers of Long-Pulse 1064-nm Nd-YAG Laser Treatments for Onychomycosis: A Pilot Study

Hindawi
BioMed Research International
Volume 2020, Article ID 1216907, 9 pages
https://doi.org/10.1155/2020/1216907

Research Article
Different Numbers of Long-Pulse 1064-nm Nd-YAG Laser
Treatments for Onychomycosis: A Pilot Study

 Rui-na Zhang ,1 Feng-lin Zhuo ,1 Dong-kun Wang ,2 Li-zhi Ma ,3
 Jun-ying Zhao ,1 and Lin-feng Li 1
 1
 Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijng 100050, China
 2
 Department of Dermatology, Beijing Evercare Jianxiang Hospital, China
 3
 Department of Dermatology, Chengdu Second People’s Hospital, China

 Correspondence should be addressed to Jun-ying Zhao; zjy63014411@aliyun.com and Lin-feng Li; zoonli@sina.com

 Received 30 April 2019; Revised 25 July 2019; Accepted 1 August 2019; Published 20 January 2020

 Academic Editor: Xin Ming

 Copyright © 2020 Rui-na Zhang et al. This is an open access article distributed under the Creative Commons Attribution License,
 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

 Purpose. To examine the benefits of different numbers of 1064-nm Nd-YAG laser treatments in patients with onychomycosis. Methods.
 This was a pilot study of patients with onychomycosis who were divided into three groups: four treatment sessions (group A), eight
 sessions (group B), and 12 sessions (group C). Only infected nails of degrees II–III (Scoring Clinical Index for Onychomycosis)
 were included. Treatment was given once a week using a long-pulse Nd-YAG 1064-nm laser. Patients were followed at 8, 16, and
 24 weeks after the first treatment. Side effects were recorded. Results. Treatments were completed for 442 nails in 102 patients. The
 efficacy rates at 8, 16, and 24 weeks were 35.5%, 38.7%, and 37.4% for group A; 31.4%, 41.7%, and 44.0% for group B; and 27.7%,
 50.0%, and 55.4% for group C, respectively. There was a significant difference in the efficacy rate at 24 weeks ( = 0.016) between
 groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed
 among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all < 0.05). No
 side effects occurred. Conclusions. The 1064-nm Nd-YAG laser had clinical benefits against onychomycosis. Higher numbers of
 treatments provided better long-term (24-week) benefits, but had no impact on the short-term outcomes. The efficacy of laser
 treatment on degree II onychomycosis was better than for degree III.

1. Introduction concentrations, and systemic oral antifungal medications are
 not applicable for some patients with abnormal liver function
Onychomycosis is a persistent fungal infection of the nail bed or low immune function [8–10]. Therefore, a new treatment
and plate and is most commonly (85–90%) caused by dermato- approach is needed.
phytes such as Trichophyton rubrum [1, 2]. The worldwide inci- Laser irradiation is an optional modality for treating onych-
dence of onychomycosis is approximately 3–5% [3, 4] and omycosis. The possible indications of laser therapy include resist-
increases with age [5]. Besides age, the risk factors are male gen- ance to or low efficacy of topical antifungals, relapsing disease,
der, athletes, diabetes, peripheral vascular diseases, and HIV and interactions and adverse events of systemic antifungals [11].
infection [1, 6]. Patients with onychomycosis may experience The lasers used for onychomycosis primarily include the carbon
significant psychosocial problems because of the appearance of dioxide (CO2), 870-nm + 930-nm, and Nd-YAG 1064-nm lasers.
the nail, particularly when fingernails are involved [7]. The CO2 laser, which was the earliest method, can directly gasify
 The treatment of onychomycosis is challenging because and degrade tissues, killing the fungi [12]. Fractional CO2 laser
the infection is embedded within the nail. Common antifungal combined with a topical antifungal agent showed good clinical
drugs for external use or oral administration used for the treat- efficacy for treating onychomycosis and it was suggested that
ment of onychomycosis include fluconazole, itraconazole, and combination therapy had a higher efficacy for treating onycho-
terbinafine [1, 2, 6], but topical antifungal agents barely pen- mycosis than did fractional CO2 laser alone [13–15]. On the
etrate the nail plate and do not achieve local therapeutic other hand, the CO2 laser is no longer used because of pain and

2 BioMed Research International

trauma. The 870-nm + 930-nm laser is a dual-wavelength Table 1: Simplified scoring clinical index of onychomycosis.
near-infrared ray, and involves a thermal effect on fungal metab-
olism for onychomycosis treatment [16]. A previous study Scoring
 Variables
showed that the long-pulse neodymium-doped yttrium alumi- 1 2 3
num garnet (Nd-YAG) laser at a wavelength of 1064 nm (Beijing Clinical
 WSO DLSO PSO or TDO
Shiji Guangtong Biotechnology Co., Ltd.) used for the treatment classification
of 154 infected nails in 33 patients could cure 52% of the nails Length of
 2/3
[17]. Many studies have confirmed that the 1064-nm Nd-YAG involvement
laser is effective against onychomycosis [11, 18–20]. The advan- Degree of
 2 mm
tages of this laser include long wavelength, high energy, simple hyperkeratosis
operation, strong penetrability, and no mutagenesis effect on cell Age of patients
 15–24 25–60 61–75
DNA [18]. (years)
 The most optimal number of treatments with the 1064-nm Location of Thumbnail or
 2–4 fingernails First toenail
Nd-YAG laser for onychomycosis remains to be validated. infected nail 2–4 toenails
Therefore, the aim of the present study was to examine the WSO: white superficial onychomycosis; DLSO: distal lateral subnail onych-
 omycosis: PSO: proximal subnail onychomycosis; TDO: total dystrophy
benefits of different numbers of 1064-nm Nd-YAG laser treat- onychomycosis.
ments in patients with onychomycosis. In order to ensure the
comparability among groups and to compare the efficacy of severity of onychomycosis, and are directly related to treatment
different degrees of severity of onychomycosis with the same efficacy and number of sessions. Another important factor influ-
number of treatment sessions, we used the Scoring Clinical encing efficacy is the growth rate of the nail, which mainly
Index of Onychomycosis (SCIO Index) and only included depends on age and location of the infected nail. Based on the
infected nails of degrees II and III. SCIO index proposed by Sergeev [21] and Hu et al. [22], we
 semi-quantified and calculated the above five factors, which were
 divided into three levels and expressed by corresponding score
2. Methods (Table 1). The severity of the infected nails was divided into five
2.1. Participants. This was a pilot study of patients with onych­ degrees: degree I: SCIO < 6, degree II: 6 ≤ SCIO < 9, degree III:
omycosis who sought treatments between 2012 and 2015. The 9 ≤ SCIO < 12, degree IV: 12 ≤ SCIO < 15, and degree V: SCIO ≥ 15.
study was approved by the ethics committee of our institution Only nails of degrees II–III were included in this study.
and was registered with the Chinese Clinical Trial Registry 2.3. Treatment. Treatment was given using a long-pulse Nd-
(ChiCTR-ONC-17012746). All patients signed the informed YAG 1064-nm laser (Beijing Shiji Guangtong Biotechnology
consent form before participation. Co., Ltd.) using the following parameters: 240–348 J/cm2,
 The inclusion criteria were: (1) 18–65 years of age; (2) typ- 3-mm spot size, 30-ms pulse duration, and 1-Hz frequency.
ical onychomycosis-related symptoms; (3) tested positive on The laser energy was adjusted based on the thickness of the
direct microscopy examination; and (4) SCIO index of 6–12, nail plate. Thicker nails required higher energy. All infected
consistent with degrees II–III. Topical antifungal agents were nails in each patient were fully covered for 2 minutes by an
prohibited for 1 month prior to participation, and systemic incrementally moving laser beam in a spiral pattern, followed
antifungal agents for 6 months. by a 2-minute pause, for three cycles. The treatment was
 The exclusion criteria were: (1) patient dropped out or performed at 1-week intervals. Patients in group A received
changed the treatment regimen or follow-up plan; (2) received four treatment sessions, those in group B received 8 sessions,
other antifungal therapy or agents affecting the outcome during and those in group C received 12 sessions.
the study; (3) showed continuous or semi-continuous nail dis-
coloration (for example, abnormal nail pigmentation caused by
 2.4. Clinical Effect Assessment. All patients were followed up
the use of topical antifungal therapy such as Castellani solution,
 at 8, 16, and 24 weeks from the first day of treatment. The
nail-coloring dyes or polishes containing magnesium and iron,
 nails were analyzed and classified into four grades according
or occupational exposure to colorants or bitumen, regardless of
 to a classification modified from Lim et al. [13], as follows:
the therapeutic or cosmetic purpose); (4) used photosensitivi-
 “complete response or cure” (the nail appears fully normal
ty-inducing medications within 6 months; (5) pregnant, (6) sub-
 from the proximal nail fold to involved nail), “significant
ungual hematoma or nevoid formation; or (7) other concomitant
 response” (>60% normal-appearing nail compared with
onychopathic-induced diseases such as nail-plate psoriasis,
 the area of the initially infected nail), “moderate response”
lichen planus, or atopic dermatitis. Those who dropped out from
 (20–60% normal-appearing nail), and “no response” (

BioMed Research International 3

 Table 2: Patients' characteristics.

Variable Group A ( = 33) Group B ( = 39) Group C ( = 30) 
Age (years) 50.40 ± 12.5 47.00 ± 10.89 49.03 ± 9.96 0.308
Duration of disease (years) 2.73 ± 1.22 2.39 ± 1.09 2.80 ± 1.51 0.338
Gender, (%) 0.949
 Male 11 (33.3%) 13 (33.3%) 11 (36.7%)
 Female 22 (66.7%) 26 (66.7%) 19 (63.3%)
Total number of infected nails, n 155 175 112
Nail thickness (mm) 0.008

4 BioMed Research International

 Figure 2: Images before and after eight treatment sessions for toenail onychomycosis.

with the two other groups ( = 0.008). The patients in group
B had more infected nails on the hands, and took less laser
energy compared with group A ( < 0.05). The clinical types
were also different among the three groups ( = 0.002). There
were no differences among the three groups regarding severity
( = 0.908).
3.2. Clinical Effect. The clinical efficacy rates at 8, 16, and
24 weeks were 35.5%, 38.7%, and 37.4% for group A; 31.4%,
41.7%, and 44.0% for group B; and 27.7%, 50.0%, and 55.4% for
group C, respectively (Table 3). More nails achieved recovery
in group C at week 24 compared with group A ( = 0.016),
but there were no differences between groups A and B, and
between groups B and C. No difference in the efficacy rate at
8 or 16 weeks was observed among the three groups. In terms
of severity (Table 4), the effective rate of nails with degree II
disease was higher than that of nails with degree III at 8, 16
and 24 weeks in all three groups (all < 0.01). Figures 1–4
present some typical cases.
 Multivariable logistic regression analysis for efficacy at
24 weeks supported that group C could achieve a better efficacy
(odds ratio [OR] = 2.589, 95% confidence interval [CI]: 1.342–
4.994, = 0.005), while degree III was a risk factor (OR = 0.107,
95%CI: 0.052–0.219, < 0.001) (Table 5). In addition, age and
nail thickness were independently associated with efficacy.
3.3. Satisfaction. In group A, four patients were very satisfied
(12.1%), six were satisfied (18.2%), 16 were slightly satisfied
(48.5%), and seven were dissatisfied (21.2%). In group B, eight
patients were very satisfied (20.5%), 19 were satisfied (48.7%), Figure 3: Images before and after 12 treatment sessions for fingernail
seven were slightly satisfied (18.0%), and five were dissatisfied onychomycosis.
(12.8%). In group C, 10 patients were very satisfied (30.3%),
five were satisfied (16.7%), 10 slightly were satisfied (30.3%),
and five were dissatisfied (16.7%) (Table 6). Satisfaction was 4. Discussion
higher for group B compared with group A ( = 0.025), The 1064-nm long-pulse Nd-YAG laser can be used to treat
without difference between groups A and C ( = 0.240), and onychomycosis, but previous studies had small sample sizes
between groups B and C ( = 0.065). and did not examine the impact of the number of treat-
 ments on the outcomes. In our study, we enrolled more
3.4. Safety. No side effects were experienced by the 102 subjects (102 patients with 442 effected nails) and included
patients. different numbers of treatment. We found that efficacy at

BioMed Research International 5

 Figure 4: Images before and after 12 treatment sessions for toenail onychomycosis.

24 weeks was significantly in group C vs. group A, but not showed cure rates of 63.5%, 57.7%, and 51.9% at 1, 3, and
between groups A and B, or between groups B and C, as 6 months, indicating that recurrence rates were higher than in
supported by the multivariable analysis. There were no dif- the present study. Of course, differences among treatment
ferences among the three groups at 8 and 16 weeks. The protocols might be responsible, at least in part, for the discrep-
results suggest that higher numbers of treatments provided ancies observed among studies.
better long-term (24-week) benefits, but the number of The response rates in this study were lower than those of
treatments had no impact on the short-term outcomes (8 oral drugs, which show cure rates of 76% for terbinafine,
and 16 weeks). In this study, we used the SCIO for evaluat- 59–63% for itraconazole, and 48% for fluconazole [1, 2, 6].
ing the severity of onychomycosis. The SCIO index was first The possible reasons could be that the laser is most effective
proposed by Sergeev et al. [21] and subsequently simplified only during heat stimulation. When heat stimulation is inter-
by Hu et al. [22]. We found that the efficacy rate was neg- rupted, the fungi gradually grow again, interrupting clinical
atively correlated with the SCIO index. The efficacy was improvements and the efficacy rate or even leading to relapse.
higher in nails of degree II (SCIO 6–8) than in degree III Antifungal agents such as terbinafine and itraconazole have
nails (SCIO 9–11) at 8, 16, and 24 weeks and in all three high affinity to keratin, resulting in higher concentrations in
groups (all < 0.05). Hence, we concluded that the long- the nails than in other body compartments. These agents can
pulse 1064-nm Nd-YAG laser is more suitable for the treat- remain in the nails for 6–9 months after drug discontinuation
ment of degree II than for degree III onychomycosis. More [23]. The combination of drugs with the 1064-nm Nd-YAG
severely infected nails (degree III) may need a combination laser should be explored [22]. Indeed, the mechanism of action
of oral drugs or other treatments to improve the efficacy of the laser is different from that of the drugs. The long-pulse
rate of the laser. The SCIO index may have a role in plan- Nd-YAG 1064-nm laser is characterized by a long wavelength,
ning laser treatment for onychomycosis. and the light energy penetrates the nail plate and reaches the
 Regarding recurrence, the numbers of nails with recur- nail bed. Chromophores in the walls of fungal cells can absorb
rence in groups A and B were 11 (7.1%) and 16 (9.1%) at week this light energy and transform it into heat to damage the cell
24, respectively, compared with two (1.8%) effected nails in wall, resulting in fungal apoptosis [24, 25]. The laser also
group C. It was presumed that the fungi might have been par- increases the temperature (to approximately 40 °C) of the nail
tially killed or inhibited after laser irradiation, but that their plate at the treatment site [16]. The fungi are damaged by
reproductive capacity was gradually restored with time. repeated heat stimulation and the fungal mitochondria pro-
Therefore, some infected nails that had improved early in the duce excess reactive oxygen species that overwhelm the pro-
study returned to baseline when treatment ended. Second, the tective capacity of the fungal cells, resulting in cell/fungal
longer the treatment, the lower the recurrence rate. According apoptosis and even death. The main advantage of antifungal
to the present study, Group C was the most effective, with a agents is the maintenance of the effect even after the end of
rate of 55.4% at 24 weeks. Therefore, it may be hypothesized treatment. On the other hand, systemic drugs are sometimes
that the number of treatments should be extended as far as contraindicated in some patients (e.g., those with liver dys-
possible and, if necessary, treatments should be given until the function), while topical drugs are associated with a compliance
infected nail is completely replaced by the new nail. A previous issue [26]. Lasers could be used as an alternative in those cases
study with the CO2 laser showed no recurrence at 3 months and in patients who do not want to take medicine. In addition,
[13], but the observation period was shorter than in the pres- combination treatments (laser and drugs) should be explored
ent study (12 vs. 24 weeks). Using the Q-switched Nd-YAG in the future.
1064-nm/532-nm laser, Kalokasidis et al. [5] showed a cure Regarding the satisfaction survey, only four (12.1%) out
rate of 95.4% at 3 months. Wanitphakdeedecha et al. [19] of 33 people were very satisfied and six (18.2%) were satisfied

6 BioMed Research International

 Table 3: Efficacy rates among the different groups.

Clinical efficacy rate Group A ( = 155) Group B ( = 175) Group C ( = 112) 
 Total 55 (35.5%) 55 (31.4%) 31 (27.7%)
 Clinical type
 DLSO 46 (42.6%) 39 (37.9%) 27 (34.2%)
 WSO 6 (30.0%) 9 (34.6%) 1 (33.3%)
 PSO 1 (11.1%) 2 (33.3%) 0%
 TDO 2 (11.1%) 5 (12.5%) 3 (11.1%)
Week 8 0.095
 Severity of infected nails
 II 47 (62.7%) 46 (52.3%) 28 (49.1%)
 III 8 (10.0%) 9 (10.3%) 3 (5.5%)
 Location of infected nails
 Fingernail 4 (23.5%) 9 (23.1%) 4 (26.7%)
 Toenail 51 (37.0%) 46 (33.8%) 27 (27.8%)
 Total 60 (38.7%) 73 (41.7%) 56 (50.0%)
 Clinical type
 DLSO 51 (47.2%) 55 (53.4%) 42 (53.2%)
 WSO 6 (30.0%) 11 (42.3%) 3 (100.0%)
 PSO 1 (11.1%) 3 (50.0%) 1 (33.3%)
 TDO 2 (11.1%) 4 (10.0%) 10 (37.0%)
Week 16 0.172
 Severity of infected nails
 II 53 (70.7%) 62 (70.5%) 37 (64.9%)
 III 7 (8.8%) 11 (12.6%) 19 (34.6%)
 Location of infected nails
 Fingernail 7 (41.2%) 13 (33.3%) 7 (46.7%)
 Toenail 53 (38.4%) 60 (44.1%) 49 (50.5%)
 Total 58 (37.4%) 77 (44.0%) 62 (55.4%)*
 Clinical type
 DLSO 51 (47.2%) 54 (52.4%) 45 (57.0%)
 WSO 6 (30.0%) 11 (42.3%) 3 (100.0%)
 PSO 0 2 (33.3%) 1 (33.3%)
 TDO 1 (5.6%) 10 (25.0%) 13 (48.2%)
Week 24 0.014
 Severity of infected nails
 II 54 (72.0%) 58 (65.9%) 41 (71.9%)
 III 4 (5.0%) 19 (21.8%) 21 (38.2%)
 Location of infected nails
 Fingernail 7 (41.2%) 13 (33.3%) 8 (53.3%)
 Toenail 51 (37.0%) 64 (47.1%) 54 (55.7%)
Group A: four sessions; Group B: eight sessions; Group C: 12 sessions. DLSO: distal lateral subnail onychomycosis; WSO: white superficial onychomycosis;
PSO: proximal subnail onychomycosis; TDO: total dystrophy onychomycosis. The clinical efficacy rate was defined as the total percentage of nails with com-
plete response and significant response. “Complete response or cure” was defined as fully normal appearing nail measured from the proximal nail fold to
involved nail; “significant response” was defined as >60% normal-appearing nail compared with the area of the initially infected nail; “moderate response” was
defined as 20–60% normal-appearing nail; and “no response” was defined as

BioMed Research International 7

 Table 4: Efficacy rates according to severity of onychomycosis in each group at different time points.

 Efficacy rate, (%)
Group Cases, 
 Week 8 Week 16 Week 24
Group A
II 75 47 (62.7%) 53 (70.7%) 54 (72.0%)
III 80 8 (10.0%) 7 (8.8%) 4 (5.0%)
 

8 BioMed Research International

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